Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971–1991)

Abstract

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly Ͼ3 cm below costal margin, 70 (35%) had platelets Ͼ600 000/mm 3 , 79 (40%) had white blood cells Ͼ12 000 mm 3 ; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value Ͻ50% in males and Ͻ45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

“…Many studies have reported on the use of pipobroman as a single agent in PV [109,110]. In one of these studies involving 163 patients, the drug was effective in more than 90% of the patients and median survival exceeded 17 years [109].…”

Patients with polycythemia vera and essential thrombocythemia with prior malignancy do not have significantly worse outcome

“…The researchers found that 270 (7%) patients who were diagnosed with cancer before being diagnosed with PV had a significantly higher frequency of thyroid, parathyroid, melanoma and skin cancers than the general population [10]. The authors concluded that patients with these cancer types should be tested for JAK2 mutations when a minimal suspicion of PV is present.…”

“…[9] Others also investigated the risk of second malignancy after the diagnosis of ET and PV and found similar results. [10-12] The clinical relevance of a diagnosed PM in patients with PV or ET is largely unknown. This led us to investigate whether PM in patients with PV and ET was associated with specific demographic or clinical characteristics and its effects on outcome of these patients.…”

Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium

“…128, 129, 130, 131 Among these second-line drugs, interferon-α is usually used for patients younger than 65 years of age and busulfan in the older age group. All three second-line drugs induce phlebotomy independence in almost all patients with PV, and response rates for thrombocytosis or leukocytosis often exceed 80%, which is superior to what was mentioned above for INCB018424.…”